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It has been heavily implied that she may be mentally ill due to her somewhat manipulative and sometimes aggressive ways. Jay wanted to divorce her after a spectacular fight they had while their kids were still in school (he taped over an episode of Dallas to record an NFL game that, ironically, featured Dallas Cowboys) but was inspired by an animatronic Abraham Lincoln exhibit at Disneyland to stick things out until Claire and Mitchell reached adulthood.

It is implied that she was initially more accepting of Mitchell's sexual orientation than Jay was when he first came out. She often uses her close relationship with Mitchell to get him to do things she doesn't want to. She is still bitter over Jay's re-marriage to Gloria and even attempted to ruin their wedding, which she convinced Mitchell to invite her to, by getting drunk and making rude and inappropriate toasts, and eventually had to be dragged out of the reception, in the process ruining the wedding cake. She is very aggressive towards Gloria, often trying to physically attack her. DeDe is also passive aggressive toward Cameron about his weight, and is often critical of Claire, especially her appearance. She also seems to be very good friends with Manny as they write letters to each other's talking about their personal issues. DeDe is also a famous author and poet.

Her antagonistic and aggressive relationship to Gloria surprisingly changes in "Arrested." When DeDe sees that Gloria is pregnant, she finds it so fantastic that her ex-husband is going to be a father again at his age. It also seemed to have fixed her uterus which she claimed was telescopic and they both bonded over Jay-bashing when DeDe tells Gloria that she was always the one having to change diapers, clean spit-up and getting baby equipment. Gloria was sympathetic explaining that it makes sense to why DeDe became so crazy to which DeDe answered "Right?".

DeDe and Jay were married to each other in the past and were obviously very happy together. One time, Jay wanted to divorce her after a spectacular fight they had when Jay taped over Dallas to record an NFL game that, ironically, featured the Dallas Cowboys) but was inspired by an animatronic Abraham Lincoln exhibit at Disneyland to stick things out until Claire and Mitchell reached adulthood.
However, Jay and DeDe are on excellent terms, even after their divorce. In "Princess Party", Jay consoled DeDe after she felt foolish to have been involved with Claire's ex-boyfriend Robbie where Jay also says that he didn't have the guts to end their marriage, with Dede replying "That's because you're a decent man." and in "The Incident", that they had grown apart for years and DeDe 'left to find herself'.

DeDe appears to be quite critical of her daughter, Claire. This most likely stems back to when Claire was an out-of-control wild child when she was a teenager. DeDe annoys Claire very much, with Claire, in return, being spiteful towards her mother. Dede is also especially critical of Claire's appearance (her blouse, on one instance in "The Incident"
However, this criticism most likely comes from the fact that Jay never helped her with their children when they were little which caused Dede to become so crazy, as stated by Gloria in "Arrested".

Initially, DeDe had animosity for Gloria because the latter married the former's ex-husband. DeDe was seen being aggressive towards Gloria during the former's first two appearances and attacking her. This antagonism continued until "Arrested" where she sees that Gloria is pregnant which causes DeDe to think of her as less trophy, more human. DeDe also found it fantastic that her ex-husband was going to be a father again at his age and also it seemed to have fixed her 'telescopic uterus'. They both bonded over Jay-bashing when DeDe revealed that he never helped her when Claire and Mitchell were babies (only for Jay to reveal that back then they were living paycheck to paycheck and that the reason he wasn't around is because he was working all the time) as well as making fun of the Pritchett pet dog Stella. Gloria was sympathetic, stating that she understood why Dede became so crazy, to which Dede answered "Right?"

Dede's relationship with her children's current lovers hasn't been completely specified.

Her relationship with Phil is kind of unknown, but in "Princess Party", Phil felt that Dede never liked him and was always wishing that Claire married her high school boyfriend Robbie, but it seems she does like him after DeDe and Robbie are seen making out.

Cam appears to have some baggage with Dede, becaus she is passive aggressive towards him about his weight, as seen when she had given him an exercise machine for Christmas.

Of all her grandchildren, DeDe's most specific relationship is with Haley. They have a very close relationship, specially when it comes to getting back at Claire for not letting Haley go places she wants (because of Claire fearing Haley will end up like her) and also Haley enjoys listening to her grandmother's stories of Claire's past.